Early exposure to bisphenol A alters neuron and glia number in the rat prefrontal cortex of adult males, but not females

Abstract

Previous work has shown that exposure to bisphenol A (BPA) during early development can alter sexual differentiation of the brain in rodents, although few studies have examined effects on areas of the brain associated with cognition. The current study examined if developmental BPA exposure alters the total number of neurons and glia in the medial prefrontal cortex (mPFC) in adulthood. Pregnant Long-Evans rats were orally exposed to 0, 4, 40, or 400 μg/kg BPA in corn oil throughout pregnancy. From postnatal days 1-9, pups were given daily oral doses of oil or BPA, at doses corresponding to those given during gestation. Brains were examined in adulthood, and the volume of layers 2/3 and layers 5/6 of the mPFC were parcellated. The density of neurons and glia in these layers was quantified stereologically with the optical disector, and density was multiplied by volume for each animal. Males exposed to 400 μg/kg BPA were found to have increased numbers of neurons and glia in layers 5/6. Although there were no significant effects of BPA in layers 2/3, the pattern of increased neuron number in males exposed to 400 μg/kg BPA was similar to that seen in layers 5/6. No effects of BPA were seen in females or in males exposed to the other doses of BPA. This study indicates that males are more susceptible to the long-lasting effects of BPA on anatomy of the mPFC, an area implicated in neurological disorders.

Long-term effects of adolescent exposure to bisphenol A on neuron and glia number in the rat prefrontal cortex: Differences between the sexes and cell type

“…We did not observed a significant effect of BPA exposure on the number of neurons. This contrasts with to the findings of Sadowski et al (2014), in which perinatal BPA exposure resulted in an increase in the number of neurons in adult male rats. This indicates a difference in vulnerability during the perinatal versus adolescent period of development.…”

“…Furthermore, it reverses the sex difference in the number of neurons in the locus coeruleus (Kubo et al, 2003). Few studies have investigated the effect of perinatal BPA exposure on areas of the brain associated with cognition, but Sadowski et al (2014) found an increase in the number of neurons in the adult medial prefrontal cortex (mPFC) in male, but not female, rats.…”

Bisphenol-A Mediated Inhibition of Hippocampal Neurogenesis Attenuated by Curcumin via Canonical Wnt Pathway

“…BPA is one of the toxic environmental and industrial EDCs, targets several tissues and organs, and causes hepatoxicity, immunotoxicity, genotoxicity, neurotoxicity, and mutagenic and carcinogenic effects [65]. BPA interferes with several molecular, neurochemical, and cellular events occurring during the normal development of the brain [66][67][68]. Recently, we have shown that BPA reduces myelination and neurogenesis in the hippocampus region via inhibition of the Wnt/β-catenin pathway, Fig.…”

Effects of developmental exposure to bisphenol A on spatial navigational learning and memory in rats: A CLARITY-BPA study

“…There is robust evidence that BPA exposure can disrupt hippocampal neural circuitry (Bowman et al, 2014; Elsworth et al, 2013; Hajszan and Leranth, 2010; Kim et al, 2011; Leranth et al, 2008a; Leranth et al, 2008b; Tiwari et al, 2014; Xu et al, 2013; Xu et al, 2014; Zhang et al, 2014). Conversely, the differential behavioral effects of BPA might be due to effects on other brain regions, such as the prefrontal, orbitofrontal, retrosplenial cortex, medial septum, ventral septum, thalamus, nucleus accumbens, and amygdala (Arias et al, 2014; Czajkowski et al, 2014; Jankowski et al, 2013; Rinaldi et al, 2012), and several other areas which have been shown to be vulnerable to BPA effects (Cao et al, 2014; Cao et al, 2013; Facciolo et al, 2002; Sadowski et al, 2014b). The behavioral disruptions may also originate from sex-dependent epigenetic changes in the brain (Jasarevic et al, 2012; Kundakovic et al, 2013; Yaoi et al, 2008).…”